The present invention relates to the detection of blood analyte levels, and is more particularly directed to a test strip which may be used to determine blood glucose levels.
It is desirable to determine and monitor blood glucose levels of patients with diabetes. Diabetic patients fall into several categories, but in all cases it is desirable to monitor, or have monitored, the blood glucose level on a frequent basis.
Self-monitoring of blood glucose by diabetic patients at home or other non-laboratory settings is increasingly common. Self-monitoring by the patient provides a means for frequent measurement of blood glucose. These measurements are important in a number of diabetic circumstances, including pregnancy, unstable diabetic conditions, propensities toward severe ketosis or hypoglycemia, an unexpected lack of the usual warning symptoms for hypoglycemia, the use of portable insulin infusion devices or multiple daily injections, and other particular circumstances.
With the increasing availability of spectroscopy and spectroscopic devices at inexpensive cost, both general and specific photometric devices have been developed which can identify chemical compounds based on their interaction with a range of electromagnetic radiation, as well as photometers specifically tailored to identify the presence and concentration of a single analyte such as glucose.
As used herein, the term "spectroscopy" refers to the analytical technique of directing incident light at a designated sample, reading the light following its interaction with the sample, and then making a determination of the contents of the sample based upon some measured differences between the incident light and the detected light. Devices for accomplishing such analysis can be referred to as "photometers", "spectrophotometers", or "spectrometers". As used herein, the term "photometer" will refer to such devices.
In the past, such devices were rather large with delicate and complicated light paths, optics capable of generating an entire spectrum of light within a given range (ultraviolet, infrared, microwave, etc.), hardware for holding liquid samples and for directing the desired frequencies of light through the samples, and often a reference "blank" which carried a solvent identical to that used in the sample in order to provide appropriate calibration. The complexity of such devices prevented their use for practical self-monitoring by individual diabetic patients.
The most common means of self monitoring currently in use incorporate a "test strip." Test strips used in the prior art typically have a substrate which carries some chemicals which change color in the presence of an analyte such as glucose. The degree of color change is dependent on the analyte level. The user can compare the resulting color which develops with a standard chart and thereby measure and monitor their blood glucose level.
In use, the patient adds a sample of blood to the test strip, waits a predetermined amount of time during which the strip changes color, and then compares the color of the strip to the standard color chart at the end of the time period. Given the difference in color perception between individuals, the characteristic poor vision of some diabetics, the difficulty with properly measuring the sample of blood, the problems in precisely timing the reaction, the continuously changing color of the test strip, variations in the test strip chemistry from batch to batch, and other inherent inaccuracies of such testing methods, the results are often unreliable. Accordingly, the development of simple photometers with which lay persons can read a digital output of the glucose level has improved home monitoring of glucose levels by diabetics.
The development of "microelectronic" technology has made photometers available to the general public at affordable prices, and where the sole purpose of the device is to determine the presence and amount of a single known analyte such as glucose, the design can be simplified. Accordingly, a number of smaller instruments are readily available as self-monitoring devices with which lay persons can attempt to diagnose their own blood chemistry.
As used in the prior art, whole blood is placed on the reagent portion of the test strip. The whole blood is reacted with enzymes, such as glucose oxidase and horseradish peroxidase, with hydrogen peroxide resulting from the reaction. Hydrogen peroxide oxidizes a chromophore, which yields a color on the test strip in proportion to the glucose concentration present in the blood. In typical use, after the reaction occurs, the test strip is placed into a commercially available photometer, which measures the color formed by the reaction. The photometer then typically translates the color into a digital display which gives a value for the level of the glucose present in the blood, normally in mg/dL.
The color change on most test strips is from a white or beige color to shades of blues and greens. Either by visual determination, or by use of the photometer, the degree of change gives an indication of the amount of analyte, such as glucose, which is present. Since the determination of blood glucose level by visual comparison of the reacted test strip with a color chart requires interpretation by the user, there are inherent deficiencies in the accuracy.
While photometers tend to be more accurate, the test strips which have used color changes to blue-green are not always clinically accurate. "Clinically accurate" is defined as glucose reading levels which yield values falling within a range which lead to clinically correct treatment decisions (Evaluating Clinical Accuracy for Self Monitoring of Blood Glucose, Clarke et al., Diabetes Care, Vol 10, No. 5, pp 622-627, 1987). In one test, the One Touch photometer was within 15% of the correct glucose level only 86% of the time, and the Accucheck III was within 15% of the correct level only 76% of the time. The American Diabetes Association has stated that self monitoring of blood glucose should, at all times, be within 15% of the results of the reference method.